The Mesenchymal Architecture of the Cranial Mesoderm of Mouse Embryos Is Disrupted by the Loss of Twist1 Function

Dev Biol. 2013 Feb 15;374(2):295-307. doi: 10.1016/j.ydbio.2012.12.004. Epub 2012 Dec 19.

Abstract

The basic helix-loop-helix transcription factor Twist1 is a key regulator of craniofacial development. Twist1-null mouse embryos exhibit failure of cephalic neural tube closure and abnormal head development and die at E11.0. To dissect the function of Twist1 in the cranial mesoderm beyond mid-gestation, we used Mesp1-Cre to delete Twist1 in the anterior mesoderm, which includes the progenitors of the cranial mesoderm. Deletion of Twist1 in mesoderm cells resulted in loss and malformations of the cranial mesoderm-derived skeleton. Loss of Twist1 in the mesoderm also resulted in a failure to fully segregate the mesoderm and the neural crest cells, and the malformation of some cranial neural crest-derived tissues. The development of extraocular muscles was compromised whereas the differentiation of branchial arch muscles was not affected, indicating a differential requirement for Twist1 in these two types of craniofacial muscle. A striking effect of the loss of Twist1 was the inability of the mesodermal cells to maintain their mesenchymal characteristics, and the acquisition of an epithelial-like morphology. Our findings point to a role of Twist1 in maintaining the mesenchyme architecture and the progenitor state of the mesoderm, as well as mediating mesoderm-neural crest interactions in craniofacial development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Craniofacial Abnormalities / genetics
  • Craniofacial Abnormalities / metabolism
  • Craniofacial Abnormalities / pathology
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / metabolism*
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental
  • In Situ Hybridization
  • Mesoderm / embryology
  • Mesoderm / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Anatomic
  • Models, Genetic
  • Neural Crest / cytology
  • Neural Crest / embryology
  • Neural Crest / metabolism
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skull / embryology
  • Skull / metabolism
  • Time Factors
  • Twist-Related Protein 1 / deficiency
  • Twist-Related Protein 1 / genetics*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Mesp1 protein, mouse
  • Nuclear Proteins
  • Twist-Related Protein 1
  • Twist1 protein, mouse